Electrical field stimulation (EFS) of rabbit ileum mounted in a flux chamber increases the luminal electrical negativity, increases the short circuit current, reduces tissue ionic conductance, and causes chloride secretion. These responses are prevented by agents which prevent neural transmission, viz., tetrodotoxin, varatrine, and Kreb's solution containing 50 mM potassium, evidence that the EFS effect is mediated by nerves or by electrically-excitable paracrine cells. The identity of the chemical transmitter is unknown, for none of the autonomic antagonists prevents the response. Of the remaining candidates, we will determine whether ATP or Substance P, among others, is the mediator. The response can be prevented by reducing the Calcium concentration of the bath fluid and by trifluoperazine, suggesting that calmodulin governs one or more steps of the response. We plan studies to determine: 1) whether EFS causes chloride secretion by increasing the permeability of the paracellular shunt (as proposed by Naftalin and Ilundain), and 2) the mechanism by which tetrodotoxin enhances the absorption of Na and Cl. We will continue studies of the effects of EFS in human intestinal epithelium, and to determine why the transverse and descending colon epithelium responds to EFS, and the ascending colon and cecum do not.